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Tacrolimus (Tac) is well established as main immunosuppressant in most immunosuppressive regimens in solid organ transplantation. Due to the narrow therapeutic window, pre dose Tac levels (C0) are monitored in all patients receiving Tac to reach optimal therapeutic levels. Tac is metabolized in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. We present a case of an African American woman who underwent a liver transplantation in which adequate Tac levels were difficult to accomplish due to differences in cytochrome P450 3A4/5 (CYP3A4/5) polymorphisms of the transplant recipient and the donor liver graft. This case report highlights that genotyping the liver transplant recipient and the donor liver graft might provide data which could be used to predict the tacrolimus metabolism post transplantation.
Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. A previous pharmacokinetic (PK) study showed that variability between patients could be partly explained by renal function and inflammatory status. The goal of this study was to combine this PK information with pharmacodynamic (PD) data, to evaluate the variability in response to midazolam and to find clinically relevant covariates that may predict PD response.
Tacrolimus is a critical dose drug and to avoid under- and overexposure, therapeutic drug monitoring is standard practice. However, rejection and drug-related toxicity occur despite whole-blood tacrolimus pre-dose concentrations ([Tac]blood ) being on target. Monitoring tacrolimus concentrations at the target site (within peripheral blood mononuclear cells; [Tac]cells ) may better correlate with drug-efficacy. The aim of this study was to (1) investigate the relationship between [Tac]blood and [Tac]cells , (2) identify factors affecting the tacrolimus distribution in cells and whole-blood, and (3) study the relationship between [Tac]cells and clinical outcomes after kidney transplantation.
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